Influenza/Pneumonia have been reported to rank eighth in the top ten causes of death in the USA. Influenza virus infection represents the most common infectious disease affecting the greatest number of people each year globally. Influenza rapidly spreads globally in seasonal epidemics and imposes considerable burden of hospitalization. Although difficult to assess globally, the World Health Organization (WHO) estimates annual epidemics morbidity of between 3 to 5 million cases of severe illness, and mortality between 250,000 to 500,000 deaths globally annually. In the US, influenza epidemics have been estimated by WHO to affect 5-15% of the US population with upper respiratory tract infections, with hospitalization and deaths mainly in high-risk groups (such as the elderly and the chronically ill), and a consequential cost of US$71-167 billion annually for the US economy. Most deaths from influenza in industrialized countries occur in elderly people over age 65. The prevalence of infections and their potential severity in terms of patient suffering, with consequential economic costs, has made their detection and treatment a priority for healthcare systems.
From the clinical perspective failure to identify patients with an influenza infection that have a higher risk of developing a severe disease delays the delivery of treatment appropriate for such high risk patients, and may have profound consequences for the recovery and long-term health of the patient. Among patients who progressed to severe disease, an average delay of 5-7 days has been consistently reported in the literature. Avoiding treatment delays in patients at risk of progressing to severe disease is critically important because timely administration of intensive care therapy is associated with a reduced risk of death from influenza. For example, it has recently been reported that a delay of one day from onset of symptom to hospital admission increased the risk of death from (H1N1) influenza by 5.5%1.
Often, influenza infection is suspected on clinical grounds alone (e.g. history of flu-like symptoms) and the individual is treated with anti-viral medications without any formal laboratory testing. The clinical decision is therefore not necessarily about whether the individual has influenza virus, but whether the individual should be admitted to hospital, or safely return home. In this context, diagnostic testing for the presence of the influenza virus may be superfluous. Instead, clinicians need a test that can assist them to quantify how adequately a patient will respond to an influenza infection, which ultimately determines the severity of the disease. The greater the severity of disease, the more likely the infected subject will deteriorate, and hence need hospital admission.
Currently, there are some laboratory methods that can reliably assess the severity of the influenza infection. One example of a method that assesses the severity of influenza infection involves testing the viral load in the airway sample as the extent of viral replication in influenza has been thought to correlate with disease severity. However, study on airway and serum samples has shown that viral loads are the same regardless of disease severity2,12. This demonstrates that the severity of an influenza infection does not necessarily correlate with the severity of the disease that manifests as a result of the infection.
Hence, for various reasons, although diagnostic tests can determine the presence or absence of the influenza virus and therefore may assist the clinician, they can be inadequate in making an impact on the clinical decisions as the presence of the virus may not always equate to an abnormal immune response which may be the actual cause of the disease progression in an infected patient.
In order to provide timely and appropriate treatment of individuals with a confirmed influenza infection or who are symptomatic of an influenza infection, a specific test that assesses disease severity or potential disease severity due to the infection is needed. Such a severity stratification tool will assist the management of such patients. It allows clinicians to identify those patients who can be safely discharged home, whilst those identified with more severe disease or have a higher risk of developing a more severe disease are admitted to the hospital for further observation and treatment. It also gives doctors the opportunity to employ preventative measures to halt or slow disease progression in patients that may be only mildly symptomatic, but would be likely to develop a severe disease.
There is a need for improved methods for assessment of individuals having, or suspected of having, influenza in order to assist the provision of prognostic and diagnostic information to aid clinical decision-making.